Effectors of the Stenotrophomonas maltophilia Type IV Secretion System Mediate Killing of Clinical Isolates of Pseudomonas aeruginosa

被引:15
作者
Nas, Megan Y. [1 ]
Gabell, Jeffrey [1 ]
Cianciotto, Nicholas P. [1 ]
机构
[1] Northwestern Univ, Sch Med, Dept Microbiol & Immunol, Chicago, IL 60611 USA
来源
MBIO | 2021年 / 12卷 / 03期
关键词
Pseudomonas aeruginosa; Stenotrophomonas; Stenotrophomonas maltophilia; bacterial competition; bactericidal activity; cystic fibrosis; lipase; peptidoglycan hydrolases; type IV secretion; GRAM-NEGATIVE BACTERIA; CRYSTAL-STRUCTURE; LIPASE; IDENTIFICATION; PNEUMONIA; PROTEINS; LUNG; MODULATION; ADAPTATION; PROTEASES;
D O I
10.1128/mBio.01502-21
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Previously, we documented that Stenotrophomonas maltophilia encodes a type IV secretion system (T4SS) that allows the organism to kill, in contactdependent fashion, heterologous bacteria, including wild-type Pseudomonas aeruginosa. Bioinformatic screens based largely on the presence of both a C-terminal consensus sequence and an adjacent gene encoding a cognate immunity protein identified 13 potential antibacterial effectors, most of which were highly conserved among sequenced strains of S. maltophilia. The immunity proteins of two of these proved especially capable of protecting P. aeruginosa and Escherichia coil against attack from the Stenotrophomonas T4SS. In turn, S. maltophilia mutants lacking the putative effectors RS14245 and RS14255 were impaired for killing not only laboratory E. coli but clinical isolates of P. aeruginosa, including ones isolated from the lungs of cystic fibrosis patients. That complemented mutants behaved as wild type did confirmed that RS14245 and RS14255 are required for the bactericidal activity of the S. maltophilia T4SS. Moreover, a mutant lacking both of these proteins was as impaired as a mutant lacking the T4SS apparatus, indicating that RS14245 and RS14255 account for (nearly) all of the bactericidal effects seen. Utilizing an interbacterial protein translocation assay, we determined that RS14245 and RS14255 are bona fide substrates of the T4SS, a result confirmed by examination of mutants lacking both the T4SS and the individual effectors. Delivery of the cloned 14245 protein (alone) into the periplasm resulted in the killing of target bacteria, indicating that this effector, a putative lipase, is both necessary and sufficient for bactericidal activity. IMPORTANCE S. maltophilia is an increasingly important opportunistic pathogen. Inherently resistant to many antibiotics, S. maltophilia is often associated with lung infection, being, among other things, a complicating factor in cystic fibrosis patients. Moreover, it is a common form of coinfection in COVID-19 patients. In these various clinical settings and in natural habitats, S. maltophilia coexists with other pathogens, including P. aeruginosa. Previously, we documented that S. maltophilia possesses a T4SS that kills other bacteria, a notable observation given that most prior work on interbacterial competition has highlighted bactericidal effects of type VI secretion systems. By utilizing approaches ranging from bioinformatics to mutant analysis to protein translocation assays, we have now identified two substrates of the Stenotrophomonas T4SS that largely mediate the killing of pathogenic P. aeruginosa. These results represent a major advance in understanding S. maltophilia, the roles of T4SSs, concepts regarding clinically relevant, interbacterial competition, and activities of bactericidal effectors.
引用
收藏
页数:23
相关论文
共 50 条
  • [31] Type IV secretion system of Brucella spp. and its effectors
    Ke, Yuehua
    Wang, Yufei
    Li, Wengfeng
    Chen, Zeliang
    [J]. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2015, 5
  • [32] Structure and Function of the Type III Secretion System of Pseudomonas aeruginosa
    Galle, Marlies
    Carpentier, Isabelle
    Beyaert, Rudi
    [J]. CURRENT PROTEIN & PEPTIDE SCIENCE, 2012, 13 (08) : 831 - 842
  • [33] The effect of pmpR on the type III secretion system in Pseudomonas aeruginosa
    Liang HaiHua
    Kong WeiNa
    Shen Tuo
    Duan JiaLi
    Duan KangMin
    [J]. CHINESE SCIENCE BULLETIN, 2012, 57 (19): : 2413 - 2418
  • [34] The type III secretion system of Pseudomonas aeruginosa: infection by injection
    Hauser, Alan R.
    [J]. NATURE REVIEWS MICROBIOLOGY, 2009, 7 (09) : 654 - 665
  • [35] Co-infection of Pseudomonas aeruginosa and Stenotrophomonas maltophilia in hospitalised pneumonia patients has a synergic and significant impact on clinical outcomes
    C. Yin
    W. Yang
    J. Meng
    Y. Lv
    J. Wang
    B. Huang
    [J]. European Journal of Clinical Microbiology & Infectious Diseases, 2017, 36 : 2231 - 2235
  • [36] Co-infection of Pseudomonas aeruginosa and Stenotrophomonas maltophilia in hospitalised pneumonia patients has a synergic and significant impact on clinical outcomes
    Yin, C.
    Yang, W.
    Meng, J.
    Lv, Y.
    Wang, J.
    Huang, B.
    [J]. EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, 2017, 36 (11) : 2231 - 2235
  • [37] Association between the Pseudomonas aeruginosa type III secretion system, antibiotic resistance and clinical features
    Wang, Juan
    Li, Yang
    Yan, Haizhong
    Luo, Xihua
    Feng, Xueqin
    Lu, Lanfen
    Wang, Weijia
    [J]. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2018, 11 (10): : 11120 - 11126
  • [38] Impact of Type III Secretion Effectors and of Phenoxyacetamide Inhibitors of Type III Secretion on Abscess Formation in a Mouse Model of Pseudomonas aeruginosa Infection
    Berube, Bryan J.
    Murphy, Katherine R.
    Torhan, Matthew C.
    Bowlin, Nicholas O.
    Williams, John D.
    Bowlin, Terry L.
    Moir, Donald T.
    Hauser, Alan R.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2017, 61 (11)
  • [39] Pseudomonas syringae type III secretion system effectors: repertoires in search of functions
    Cunnac, Sebastien
    Lindeberg, Magdalen
    Collmer, Alan
    [J]. CURRENT OPINION IN MICROBIOLOGY, 2009, 12 (01) : 53 - 60
  • [40] Structural Basis of Lipid Targeting and Destruction by the Type V Secretion System of Pseudomonas aeruginosa
    da Mata Madeira, Paulo Vinicius
    Zouhir, Samira
    Basso, Pauline
    Neves, David
    Laubier, Aurelie
    Salacha, Richard
    Bleves, Sophie
    Faudry, Eric
    Contreras-Martel, Carlos
    Dessen, Andrea
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2016, 428 (09) : 1790 - 1803